A new model of paraplegia due to spinal cord ischemia and its use to investigate iron chelator treatment
Abstract
The development of paraplegia following surgery to correct an aortic aneurysm is a devastating phenomenon. The injury arises from the fact that the collateral blood flow to the spinal cord is inadequate in some patients to prevent ischemia to the distal spinal cord subsequent to aortic cross-clamping. One objective of this study was to evaluate the sensitivity and specificity of the motor-evoked potential (MEP) in monitoring the structural and functional integrity of the spinal cord during a transient period of aortic occlusion. A second objective of this research was to develop a new model of spinal cord ischemia in which pharmacological interventions could be tested. The model was used to evaluate the extent to which iron-mediated free radical reactions contribute to tissue injury by administering iron-chelator drugs. A model of spinal cord ischemia was developed in which a 100% incidence of paraplegia was achieved by using the amplitude reduction of the MEP to determine the duration of aortic occlusion. The model included an analysis of spinal cord blood flow, histological damage, MEP response, somatosensory-evoked potential (SSEP) response, and neurological outcome. Following aortic occlusion, the MEP signal recorded at segmental level L$\sb2$ decreased to 20% of its control amplitude in 21.0 $\pm$ 6.6 minutes. In contrast, the SSEP disappeared before the MEP L$\sb2$ signal in all dogs, with a mean amplitude reduction time of 10.9 $\pm$ 5.6 minutes. The presence of the MEP signal 24 hours after the period of aortic occlusion in paraplegic animals from the control group revealed that the return of the evoked potential signal was not of prognostic value in predicting motor function recovery. The results of our study revealed a positive correlation between the amplitude reduction of the spinal cord MEP signal and both spinal cord ischemia and histopathological damage. The model was used to test the hypothesis that treatment with an iron-chelator agent would minimize structural and functional damage by inhibiting the production of free radicals via iron-catalyzed reactions. Treatment of two different groups of dogs with deferoxamine and L1, respectively, significantly reduced the neurological deficits and the neuronal damage in both groups. The ability of a water-soluble iron chelator such as deferoxamine to confer protection to the spinal cord during and after a period of ischemia is consistent with the hypothesis that the CNS microvasculature contributes significantly to the production of free radicals via iron-catalyzed reactions which ultimately lead to tissue damage and neurological deficits.
Degree
Ph.D.
Advisors
Tacker, Purdue University.
Subject Area
Anatomy & physiology|Animals|Surgery|Biomedical research
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